The goal of this application is to develop optimal methods for estimating atherosclerotic plaque deformation through the cardiac cycle from ultrasound videos of the carotid artery. The proposed methodology will allow clinicians to visualize how different atherosclerotic plaque components deform throughout the cardiac cycle and to identify how these deformations correlate with stroke risk assessment. Our methodology will provide an innovative system for accurately stratifying risk of stroke from plaque deformations. As the preliminary results indicate, we will be able to discriminate between the large deformations of hypoechoic (dark), unstable plaque regions and the small deformations of hyperechoic (bright), stable plaque regions. By quantifying the deformations over the entire cardiac cycle, we will be able to monitor large changes in the behavior of the different plaque components. These results will advance our understanding of how plaque instability can lead to increased risk of stroke. The demonstration of this technique as part of computer-aided diagnostic system will have major commercial interest with vendors of ultrasound equipment and vascular specialists. The visualization of the instabilities associated with the hypoechoic plaque regions, which include lipid regions, will provide a clear, early indication of how obesity can lead to stroke. Early detection can directly contribute to reducing the current ratio that attributes 1 out of every 16 US deaths to stroke (World Health Organization). Last year, over 6 million cardiovascular-related deaths had atherosclerosis as the underlying cause (American Heart Association). The business opportunities are significant in the sense that this new, inexpensive, clinical methodology can be widely deployed as a standard screening tool for the at risk population. In collaboration with our clinical team, we will develop the clinical acquisition protocol for use with standard 2D ultrasound devices. The innovation in the proposed approach comes from the development of several new methods developed by the principal collaborators. This includes the development of methods for standarding the ultrasound image acquisition, plaque component estimation, m-mode estimation, image segmentation and robust motion and deformation estimation. The focus of our application is in the development of new methods for robust motion and deformation estimation. The basic idea is to use high values of cross-correlation to get coarse but reliable motion estimates and use these estimates to help tune our optical-flow, pixel-based estimates. This hierarchical approach brings the well-established robustness of the cross-correlation approach to the fine resolution, pixel based estimates of the optical flow methodology.